Uso del esquema Scottish and Newcastle Anti-Emetic Pretreatment (SNAP) en la recuperación de una intoxicación por sobredosis masiva de acetaminofén (paracetamol) con injuria hepática aguda - Reporte de caso

Acetaminophen is a drug widely used in the world and easily accessible due to its antipyretic, analgesics characteristics, among others (1); however, exposure to toxic doses causes organic damage and even death. We present the case of an 18-year-old female patient who ingested 40 grams of acetaminophen and developed severe liver dysfunction, being treated with N-acetylcysteine (NAC) antidotal therapy according to the simplified scheme: Scottish and Newcastle Anti-emetic Pretreatment Paracetamol Poisoning Study Regimen (SNAP), presenting improvement in the clinical course and decrease in liver profiles, coagulation disorder, INR and resolution of the condition.

El acetaminofén es un fármaco ampliamente usado en el mundo y de fácil acceso por sus características antipiréticas, analgésicas, entre otras (1); sin embargo la exposición a dosis tóxicas produce daños a nivel orgánico e incluso la muerte. Presentamos el caso de una paciente mujer de 18 años que ingirió 40 gramos de acetaminofén y desarrolló injuria hepática severa, siendo tratada con terapia antidotal de N-acetilcisteína (NAC) según el esquema simplificado: Scottish and Newcastle Anti-Emetic Pretreatment Paracetamol Poisoning Study Regimen (SNAP), presentando mejoría del curso clínico y disminución de los perfiles hepáticos, trastorno de coagulación, INR y resolución del cuadro.

Inhibitory effects of N-acetylcysteine and salubrinal on apoptosis of retinal pigment epithelial cells induced by all-trans-retinoic acid / 中华实验眼科杂志

Objective:To observe the effect of the antioxidant N-acetylcysteine (NAC) and selective endoplasmic reticulum stress response inhibitor salubrinal on the apoptosis of retinal pigment epithelial cells induced by all-trans-retinoic acid (ATRA).Methods:Human ARPE-19 cell line was used as the experimental cell line, and was divided into normal control group cultured with complete medium, model control group cultured with complete medium containing 10 μmol/L ATRA, NAC treatment group cultured with complete medium containing 10 μmol/L ATRA+ 5 mmol/L NAC, salubrinal group cultured with complete medium containing 10 μmol/L ATRA+ 40 μmol/L salubrinal, NAC+ salubrinal group cultured with complete medium containing 10 μmol/L ATRA+ 5 mmol/L NAC+ 40 μmol/L salubrinal.After 24-hour culture, apoptosis rate, multicaspase level and reactive oxygen species (ROS) level of ARPE-19 cells were detected by flow cytometry.The expressions of vascular endothelial growth factor A (VEGF-A), C/EBP-homologous protein (CHOP), cleaved-caspase 3 in cells were detected by Western blot.Results:There were significant differences in the apoptosis rate, multicaspase and ROS levels among the five groups ( F=113.23, 602.41, 160.39; all at P<0.001). The apoptosis rate, multicaspase and ROS levels of normal control group, NAC treatment group, salubrinal group and NAC+ salubrinal group were significantly lower than those of model control group (all at P<0.05). There were significant differences in the expression levels of VEGF-A, CHOP and cleaved-caspase 3 among the five groups ( F=24.62, 36.35, 60.25; all at P<0.001). The protein expression levels of VEGF-A, CHOP and cleaved-caspase 3 of normal control group, NAC treatment group, salubrinal group and NAC+ salubrinal group were significantly lower than those of model control group (all at P<0.05). Conclusions:ATRA can induce RPE cells to produce oxidative stress and endoplasmic reticulum stress injury, which leads to apoptosis.NAC and salubrinal can effectively reduce the RPE cell apoptosis by inhibiting stress response.

Mucin levels in glands of the colonic mucosa of rats with diversion colitis subjected to enemas containing sucralfate and n-acetylcysteine alone or in combination

ABSTRACT Purpose: To evaluate the tissue content of neutral and acidic mucins, sulfomucins and sialomucins in colonic glands devoid of intestinal transit after enemas containing sucralfate and n-acetylcysteine alone or in combination. Methods: Sixty-four rats underwent intestinal transit bypass. A colonic segment was collected to compose the white group (without intervention). After derivation, the animals were divided into two groups according to whether enemas were performed daily for two or four weeks. Each group was subdivided into four subgroups according to the substance used: control group: saline 0.9%; sucralfate group (SCF): SCF 2 g/kg/day; n-acetylcysteine group (NAC): NAC 100 mg/kg/day; and SCF+NAC group: SCF 2 g/kg/day + NAC 100 mg/kg/day.Neutral and acidic mucins were stained by periodic acid-Schiff and alcian-blue techniques, respectively. The distinction between sulfomucins and sialomucin was made by the high alcian-blue iron diamine technique. The content of mucins in the colonic glands was measured by computerized morphometry. The inflammatory score was assessed using a validated scale. The results between the groups were compared by the Mann-Whitney's test, while the variation according to time by the Kruskal-Wallis' test (Dunn's post-test). A significance level of 5% was adopted. Results: There was reduction in the inflammatory score regardless of the application of isolated or associated substances. Intervention with SCF+NAC increased the content of all mucin subtypes regardless of intervention time. Conclusions: The application of SCF+NAC reduced the inflammatory process of the colonic mucosa and increased the content of different types of mucins in the colonic glands of segments excluded from fecal transit.

Efficacy of atomization with budesonide, salbutamol, and acetylcysteine in the adjuvant treatment of bronchopneumonia in children / 中国基层医药

Objective:To investigate the efficacy of atomization with budesonide, salbutamol, and acetylcysteine in the adjuvant treatment of bronchopneumonia in children.Methods:Seventy-two children with bronchopneumonia admitted to Huaiyuan Jingtu Hospital from July 2021 to June 2022 were retrospectively included in this study. These children were divided into BS and BSY groups according to different treatment methods. Based on conventional treatment, the BS group was given atomization treatment with budesonide and salbutamol, and the BSY group was given atomization treatment with budesonide, salbutamol, and acetylcysteine. After two courses of treatment, clinical efficacy, duration to improvements in symptoms and signs, adverse drug reactions, and changes in serum C-reactive protein and procalcitonin levels after treatment relative to those before treatment were compared between the two groups. The optimal medication plan was investigated.Results:The total response rate in the BSY group was 91.67% (33 cases/36 cases), which was significantly higher than 72.22% (26/36) in the BS group ( χ2 = 4.59, P = 0.032). The incidence of adverse drug reactions in the BSY group was 11.11% (4/36), which was significantly lower than 19.44% (7/36) in the BS group ( χ2 = 0.96, P = 0.326). After treatment, the levels of C-reactive protein and procalcitonin in the BSY group were (5.86 ± 5.66) mg/L and (2.59 ± 0.74) μg/L, respectively, which were lower than (15.64 ± 5.85) mg/L and (4.71 ± 0.93) μg/L in the BS group ( t = 7.20, 10.70, both P < 0.001). The durations to the disappearance of symptoms and signs including fever, cough, lung rales, and X-ray lung shadow in the BSY group were significantly shorter compared with the BS group ( t = 11.85, 4.19, 2.72, 2.39, all P < 0.05). Conclusion:Atomization with budesonide, salbutamol, and acetylcysteine in combination for the adjuvant treatment of bronchopneumonia in children can quickly relieve the clinical symptoms of children, improve the lung signs, reduce the degree of inflammation, and has a remarkable therapeutic effect on bronchopneumonia in children.

Comparison of Outcomes Between High and Standard Dose of N-acetylcysteine in Prevention of AKI in Patients with CKD

Background: Patients with chronic kidney disease (CKD) are at a common risk for contrast-induced acute kidney damage (CI-AKI) because of various complications. Intravenous N-acetylcysteine (NAC) in high doses (1200mg) is considered more effective than its conventional dose (600mg) to prevent CIN and related complications. Objective: The study aimed to compare the effectiveness of high dose versus standard dose of intravenous N-acetylcysteine (NAC) in the prevention of Acute Kidney Injury in patients with chronic kidney disease.Material & Methods:A total of 60 (sixty) patients diagnosed with CKD went to coronary angiography and/or percutaneous coronary intervention (PCI) were selected by simple random technique and categorized into two groups – Group A (30 patients) received high dose NAC (1200mg) and Group B (30 patients) – received standard dose NAC (600mg). For evaluation of renal damage serum creatinine level for at least >3 months, renal imaging revealed bilateral small echogenic kidneys, eGFR (<60 to 15ml/min/1.73m², measured by MDRD formula) and also by ACR >30 mg/gm, associated with IHD, admitted for percutaneous intervention (PCI) were taken in account. Statistical analysis was done by SPSS version 20 with taking 95% confidence interval. The quantitative data were expressed as mean and standard deviation and qualitative data were expressed as frequency distribution and unpaired t-test, Chi-square test, and Fisher exact analytic test were done.Results:The observed mean age group of the patients was 65 ± 8 years and 62 ± 7 years in group A and group B respectively with male predominance in both groups. Primary renal disease diabetic nephropathy (DN) more (36.66%) in group A than in group B (30.00%) but patients with Hypertensive nephropathy were the same (33.33%) in both groups. After interventions, S. Creatinine (mg/dl) level, e, GFR (ml/min/1.73m²), were statistically significant in cases of group A patients (P-value 0.001& 0.003 correspondingly) compared to group B Patients (P-value 0.075 & 0.001 respectively). Again, the mean of pre-intervention S. Creatinine was 1.7 ±0.5 in group A whereas this was 1.9 ± 0.8 (p-value, 0.599) in group B and after 48 hours of intervention this was 1.6 ± 0.5 and 2.0 ± 0.5 (p-value, 0.697) In group A and group B respectively. Overall, no patients were detected with nephropathy for high dose NAC whereas 27 (90%) out of 30 had developed CIN in standered dose.Conclusion:High-dose N-acetylcysteine (1200mg) is more potent and effective than the standard dose (600mg) in reducing contrast-induced acute kidney injury (CI-AKI) in patients with CKD.

Perfil epidemiológico de pacientes intoxicados con acetaminofén con intenciones suicidas / Epidemiological profile of patients intoxicated with acetaminophen for suicidal purposes / Perfil epidemiológico de pacientes intoxicados com acetaminofen (Paracetamol) com intenções suicidas

Objetivo: este estudio busca describir los individuos evaluados por sobredosis de acetaminofén entre 2019 y 2020 en un centro de referencia de trasplante hepático en Colombia. Metodología: estudio derivado del análisis secundario de historias clínicas entre el 1.º de enero de 2019 y el 31 de diciembre de 2020. Los criterios de inclusión abarcan individuos con ingestión aguda y voluntaria de dosis tóxicas de acetaminofén (>4 g/día). Resultados: sesenta y tres casos, 68% mujeres, 67% menores de 18 años y 54% estudiantes. Reportó historia personal de enfermedad psiquiátrica el 60% y el 35% al menos un intento de suicidio previo. La mediana de dosis de acetaminofén fue 15g, 46% refirieron co-ingesta de otras sustancias y 13% estaba bajo efecto de sustancias psicoactivas. El 57% tenía la intención clara de suicidarse, así como 81% vomitó antes de acudir al servicio de urgencias, 22% recibió medidas de descontaminación y 10% no recibió N - acetilcisteína. Quince individuos desarrollaron lesión hepática aguda, nueve con criterios de severidad. Conclusiones: la población era predominantemente joven, la historia de enfermedad psiquiátrica fue muy prevalente y la mayoría refirieron un evento vital que explicara el comportamiento impulsivo de consumo. Ninguno desarrolló criterios para trasplante hepático, lo cual podría explicarse por la edad de los individuos, los episodios de vómito temprano, y la ausencia de enfermedad hepática crónica o de consumo de sustancias hepatotóxicas.

Objective: this study aims to describe patients with overdose intake of acetaminophen between 2019 and 2020 at a reference center for liver transplantation in Colombia. Methodology: study derived from a secondary analysis of the clinical records between January 1st, 2019, to December 31st, 2020. Inclusion criteria were individuals with voluntary acute ingestion of toxic doses of acetaminophen (>4 g/day). Results: sixty-three cases, 68% women, 67% <18-year-old, and 54% students. 60% had personal history of psychiatric illness and 35% reported at least one previous suicide attempt. The median dose of acetaminophen was 15g, 46% referred to co-ingestion with other substances and 13% were under the effect of any psychoactive substance. 57% had a clear intention of suicide. 81% vomited before the arrival to the emergency room, 22% received decontamination intervention with gastric lavage or activated charcoal, and 10% did not receive any dose of N-Acetylcysteine. Fifteen individuals developed an acute liver injury, nine with severity criteria. Conclusions: the population was predominantly young, the personal history of psychiatric disease was highly prevalent, and most of the cases referred a vital event that explains the impulsive behavior in acetaminophen consumption. None developed criteria for liver transplantation, and this could be explained by the young age of the individuals, the episodes of early vomiting, and the absence of chronic liver disease or hepatotoxic substance consumption.

Objetivo:este estudo busca descrever os indivíduos avaliados por sobredose de acetaminofen entre 2019 e 2020 num centro de referência de transplante hepático na Colômbia. Metodologia: estudo derivado da análise secundário de histórias clínicas entre o dia 1.º de janeiro de 2019 e 31 de dezembro de 2020. Os critérios de inclusão abrangem indivíduos com ingestão aguda e voluntária de dose tóxicas de acetaminofen (>4 g/dia).Resultados:sessenta e três casos, 68% mulheres, 67% menores de 18 anos e 54% estudantes. Reportou história pessoal de doença psiquiátrica, 60% e 35% pelo menos uma tentativa de suicídio prévio. A média de dose de acetaminofen foi de 15g, 46% referiram com ingestão de outras sustâncias e 13% estava sob efeito de sustâncias psicoativas. 57% tinham a intenção clara de suicidar-se, assim como 81% vomitou antes de acudir ao serviço de urgências, 22% receberam medidas de descontaminação e 10% não recebeu N - acetilcisteína. Quinze indivíduos desenvolveram lesão hepática aguda, nove com critérios de severidade. Conclusões: a população era predominantemente jovem, a história de doençapsiquiátrica foi muito prevalente e a maioria referiram um evento vital que explicasse o comportamento impulsivo de consumo. Nenhum desenvolveu critérios para transplantehepático, o qual se poderia explicar pela idade dos indivíduos, os episódios de vómito precoce, e a ausência de doença hepática crónica ou de consumo de sustâncias hepatotóxicas.

The protective effect and mechanism of N-acetylcysteine on acute kidney injury by up-regulating Sirtuin3 protein expression in septic mice / 中华急诊医学杂志

Objective:To explore the protective effect and mechanism of the antioxidant N-acetylcysteine (NAC) regulating silent information regulator 3 (Sirt3) on acute kidney injury (AKI) in septic mice.Methods:Male C57BL/6 mice were randomly ( random number) divided into the sham operation group (sham), cecal ligation and perforation group (CLP), CLP + NAC (50 mg/kg) and CLP + NAC (100 mg/kg) groups, with 10 mice in each group. The mice were sacrificed 24 h after CLP, and blood and kidney tissue samples were collected. HE staining was used to evaluate the pathological damage of the kidney tissue of mice in each group. ELISA was used to detect serum creatinine (Scr), urea nitrogen (BUN), kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated apolipoprotein (NGAL) levels. Immunohistochemistry was used to detect the expression of Sirt3 protein in kidney tissue. RT-qPCR was used to detect the level of Sirt3 mRNA. Mitochondrial damage of renal tubular epithelial cells was observed under transmission electron microscope, and the mitochondrial density was calculated. Meanwhile, the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and malondialdehyde (MDA) in the renal cortex were also detected. Results:Compared with the sham group, in the CLP group, the pathological damage of renal tissue was significantly aggravated ( P<0.001), and the levels of renal function indicators (Scr, BUN, KIM-1 and NGAL) were all increased significantly (all P<0.001). The protein and mRNA expression of Sirt3 were all significantly decreased (all P<0.001), the mitochondrial structure damage of renal tubular epithelial cells was increased, and the mitochondrial density was significantly decreased ( P<0.001). The levels of antioxidant enzymes (SOD, GSH-Px and CAT) in the renal cortex were all significantly decreased (all P<0.001), while the lipid peroxide MDA was significantly increased ( P<0.001). Compared with the CLP group, the renal injury score and renal function indexes (Scr, BUN, KIM-1 and NGAL levels) in the 50 mg/kg NAC pretreatment group were decreased, and the levels of SOD, GSH-Px and CAT in renal tissue were increased, but the differences were not significant. However, pretreatment with 100 mg/kg NAC significantly reduced the pathological damage of kidney tissue caused by CLP ( P<0.001), and significantly decreased the levels of Scr, BUN, KIM-1 and NGAL (all P<0.001). The expression of Sirt3 protein [(50.20±2.79) vs.(20.00±0.75), P<0.001] and mRNA [(0.57±0.07) vs. (0.41±0.07), P<0.001] were all significantly increased. The mitochondrial structure of renal tubular epithelial cells was more stable, and the mitochondrial density was significantly increased [(0.60±0.05) vs. (0.43±0.06), P<0.001]. The levels of SOD [(67.37±3.79) U/mg vs. (21.09±0.89) U/mg, P<0.001], GSH-Px [(265.61±9.61) U/mg vs. (180.00±3.31) U/mg, P<0.001] and CAT [(8.58±0.65) U/mg vs. (5.19±0.58) U/mg, P<0.001] were all significantly increased, while the expression level of MDA was significantly reduced [(40.36 ±1.79) vs. (83.81 ±1.70), P<0.001]. Conclusions:NAC can significantly reduce renal pathological damage, improve renal function, maintain mitochondrial structure stability and reduce oxidative stress levels in septic mice by up-regulating Sirt3 protein expression, and has a significant protective effect on CLP-induced AKI.

Hepatotoxicidad por talidomida: caso clínico y revisión de la literatura / Hepatotoxicity by thalidomide: case report and literature review

La talidomida fue desarrollada e introducida al mercado por los laboratorios Grünenthal en 1953, siendo usada principalmente como sedante y también para el tratamiento de las náuseas durante el embarazo. Los informes dan cuenta de aproximadamente 10.000 niños que nacieron con focomelia, dando lugar a la denominada "tragedia de la talidomida", que obligó a su retiro del mercado en 1962. Luego de casi 60 años, es nuevamente utilizada en otros campos de la medicina, entre ellos, para el tratamiento de la lepra y del mieloma múltiple, debido a sus propiedades antinflamatorias, inmunomoduladoras y antiangiogénicas, con expresas advertencias sobre su utilización durante el embarazo; no obstante, con su nuevo uso han sido reportados múltiples efectos adversos, entre los que se encuentra la hepatitis aguda o crónica inducida por este fármaco. Se presenta el caso de una paciente de 34 años con lepra, que estaba en tratamiento con talidomida desde hacía 4 años para combatir las lesiones de piel asociadas a esta enfermedad. Presentó malestar general, vómito, pérdida de peso, artralgias, ictericia, edemas de miembros inferiores, ascitis, coluria y acolia. Se sospechó toxicidad por talidomida, por lo que se suspendió su uso, y se trató con ácido ursodesoxicólico y N-acetilcisteína con mejoría sintomática y de laboratorio, desde la primera semana hasta los 41 días de seguimiento. Las entidades clínicas para las cuales se aprobó talidomida en 1998, pueden traer nuevos problemas y desafíos clínicos. Este caso muestra hepatotoxicidad crónica por talidomida, situación que hasta el momento no se había reportado en la literatura.

Thalidomide was developed and introduced to the market by Grünenthal laboratories in 1953, being used mainly as a sedative and also for the treatment of nausea during pregnancy. Reports give account of approximately 10,000 children who were born with phocomelia, giving rise to the so-called "thalidomide tragedy", which forced its withdrawal from the market in 1962. After almost 60 years, it is usedagain in other fields of medicine, including the treatment of leprosy and multiple myeloma, due to its anti-inflammatory, immunomodulatory and anti-angiogenic properties, with clear warnings about its use during pregnancy; however, multiple adverse effects have been reported in patients with leprosy and multiple myeloma, including acute or chronic hepatitis. We present the case of a 34-year-old patient with leprosy, who had been on thalidomide therapy for 4 years to treat skin lesions associated with this disease. She presented general malaise, vomiting, weight loss, arthralgia, jaundice, lower limb edema, ascites, choluria and acholia. Thalidomide toxicity was suspected, so its use was suspended, and treatment with ursodeoxycholic acid and N-acetylcysteine was initiated, with symptomatic and laboratory improvement from the first week up until 41 days of follow-up. The new range of medical conditions for which thalidomide was approved for in 1998 may bring clinical challenges. This case shows chronic hepatotoxicity due to thalidomide, a situation that had not been reported previously in the literature.

Effects of N-acetylcysteine on endoplasmic reticulum stress and oxidative stress in cerebral micro-vascular endothelial cells / 中华行为医学与脑科学杂志

Objective:To investigate the effect of N-acetylcysteine (NAC) on endoplasmic reticulum stress (ERS) and oxidative stress(OS) induced by tunicamycin (Tm) and its mechanism.Methods:Mouse derived brain microvascular endothelial cells cultured in vitro were divided into control group (normal cell culture), TM group (cells were intervened with 5 μg/mL Tm for 24 h), NAC + TM group (cells were pretreated with 1 mmol/L NAC for 1 h, then were intervened with 5 μg/mL Tm for 24 h) and NAC group (cells were intervened with 1 mmol/L NAC for 24 h) according to different intervention methods.CCK-8 and FITC-Annexin V/PI were used to detect the survival rate and apoptosis rate of cells.Western blot was used to detect the expression of GRP78、CHOP、p-eNOS and caspase-12 protein. Laser confocal microcopy was used to detect the expression of ROS, and colorimetry was used to detect the activity of MDA and SOD.Results:There were significant differences in apoptosis rate and survival rate among the four groups ( F=62.57, 35.00, both P<0.05). The apoptosis rate of TM group ((25.49±1.55)%) was higher than that of Control group ((13.76±1.48)%)( P<0.01), while the apoptosis rate of NAC+ TM group ((17.65±1.00)%) was lower than that of TM group ( P<0.01). The survival rate of TM group ((66.33±5.69)%) was lower than that of Control group ((100.00±2.12)%)( P<0.01), while the survival rate of NAC+ TM group ((85.67±4.04)%) was higher than that of TM group ( P<0.01). Western blot showed that there were significant differences in the expression levels of GRP78、CHOP and p-eNOS among the four groups ( F=32.39, 68.66, 13.12, all P<0.01). The expression levels of GRP78 and CHOP protein in TM group were higher than those of Control group (both P<0.05), while the expression level of p-eNOS was lower than that of Control group ( P<0.01). The expression levels of GRP78 and CHOP protein in NAC+ TM group were lower than those of TM group (both P<0.05), while the expression level of p-eNOS was higher than that of TM group ( P<0.01). There was no significant difference in the expression level of caspase-12 protein among the four groups ( F=0.33, P>0.05). Laser confocal showed that there was significant difference in the average fluorescence intensity of ROS among the four groups ( F=77.66, P<0.01). The average fluorescence intensity of ROS in TM group (32.67±1.53) was higher than that in Control group (12.67±2.08) and NAC+ TM group (18.33±1.53) (both P<0.01). Colorimetry showed that there were significant differences in the activity of SOD and the concentration of MDA among the four groups ( F=40.53, 34.99, both P<0.01). The results of colorimetry showed that the activity of SOD in TM group((41.60±1.53)U/mg) was lower than that in Control group((65.39±4.60)U/mg) and NAC+ TM group((58.72±1.64)U/mg)(both P<0.01). The concentration of MDA in TM((2.27±0.11)μmol/mg) group was higher than that in Control group((1.39±0.13)μmol/mg) and NAC+ TM group((1.44±0.11)μmol/mg) (both P<0.01). Conclusion:NAC can reduce Tm-induced apoptosis of cerebral micro-vascular endothelial cells, which may be related to its inhibition of ERS/ OS-related pathways.

N-acetylcysteine prevents contrast-induced nephropathy following percutaneous coronary intervention in elder patients with coronary heart disease complicated with moderate to severe renal dysfunction: a clinical efficacy study / 中华老年医学杂志

Objective:To investigate the preventive effects of intravenous N-acetylcysteine(NAC)administration on contrast-induced nephropathy(CIN)following coronary intervention in elder patients with coronary heart disease(CHD)complicated with moderate to severe renal dysfunction.Methods:In this retrospective study, 242 elderly patients with CHD and moderate to severe renal insufficiency hospitalized in the Department of Cardiology of the First Affiliated Hospital of Nanjing Medical University and undergone coronary angiography from January 2018 to February 2022 were included and divided into two groups: the treatment group(100 cases)receiving NAC plus a continuous intravenous drip of 0.9% sodium chloride solution before and after surgery and the control group(142 cases)treated with only a continuous intravenous drip of 0.9% sodium chloride solution.To ensure the comparability of important baseline data between the two groups, a 1∶1 propensity score matching analysis was used, and 70 patients in each group were finally included.Pre-and post-operative serum creatinine(Scr)and blood urea nitrogen(BUN)values were recorded, the endogenous creatinine clearance(Ccr)and estimated glomerular filtration rate(eGFR)were calculated, and the incidences of CIN and changes in renal function indicators were compared between the two groups.Results:After coronary intervention, the incidence of CIN in the treatment group was significantly lower than that in the control group(1/70 or 1.4% vs.8/70 or 11.4%, P=0.033). In the treatment group, Scr[(186.01±36.62)μmol/L vs.(195.84±36.39)μmol/L, t=4.957, P<0.001]and BUN[(13.97±2.89)mmol/L vs.(14.84±2.85)mmol/L, t=5.206, P<0.001]decreased, while Ccr[(31.84±6.54)ml/min vs.(30.08±5.65)ml/min, t=-5.076, P<0.001]and eGFR[(31.60±6.93)ml·min -1·1.73m -2vs.(29.82±5.92)ml·min -1·1.73m -2, t=-5.200, P<0.001]increased, compared with pre-operative levels.In the control group, Scr[(186.65±27.28)μmol/L vs.(182.53±22.08)μmol/L, t=-1.783, P=0.079]and BUN[(17.57±3.33)mmol/L vs.(17.13±3.35)mmol/L, t=-2.234, P=0.029]increased, but Ccr[(30.57±6.37)ml/min vs.(31.06±6.01)ml/min, t=1.435, P=0.156]and eGFR[(30.76±6.46)ml·min -1·1.73m -2vs.(31.26±6.02)ml·min -1·1.73m -2, t=1.436, P=0.156]decreased, compared with pre-operative levels, and there was no significant difference except BUN(all P>0.05). Conclusions:For elderly patients with coronary heart disease complicated with moderate to severe renal insufficiency, the use of NAC before and after coronary intervention can reduce the risk of CIN and help improve renal function.

Intoxicación aguda por acetaminofén en atención primaria / Acute Acetaminophen Intoxication in Primary Care / Intoxicação aguda por acetaminofeno na atenção primária

Resumen: El acetaminofén es un medicamento analgésico y antipirético considerado como seguro y eficaz. Debido a esto, en Colombia es de venta libre y ampliamente utilizado tanto en niños como en adultos. Por su fácil acceso, la intoxicación por acetaminofén es un evento frecuente, por lo que los médicos de atención primaria deben tener conocimiento acerca de su diagnóstico y manejo, además de los factores de riesgo para el desarrollo de falla hepática y las indicaciones para remitir a los pacientes a los servicios especializados. El objeto de este artículo es orientar al personal de atención primaria en salud acerca de la fisiopatología, el diagnóstico y el tratamiento de esta intoxicación.

Abstract: Acetaminophen is an analgesic and antipyretic medication considered safe and effective. Because of this, in Colombia it is freely available and widely used in both children and adults. Due to its easy access, acetaminophen intoxication is a frequent event, so primary care physicians must be knowledgeable about its diagnosis and management. In addition to the risk factors for the development of liver failure and the indications for referring patients to specialized services. The purpose of this article is to guide primary health care personnel about the pathophysiology, diagnosis and treatment of this intoxication.

Resumo: O acetaminofeno é um medicamento analgésico e antipirético considerado seguro e eficaz. Por isso, na Colômbia é over-the-counter e amplamente utilizado em crianças e adultos. Por seu fácil acesso, a intoxicação por acetaminofeno é um evento frequente, é por isso que os médicos da atenção primária devem estar cientes de seu diagnóstico e manejo. Além dos fatores de risco para o desenvolvimento de insuficiência hepática e indicações de encaminhamento aos pacientes para serviços especializados. O objeto deste artigo é guiar á equipe da atenção primária á saúde sobre a fisiopatologia, diagnóstico e tratamento dessa intoxicação.

Rol protector de N-acetilcisteína en la ototoxicidad inducida por cisplatino en pacientes con cáncer de cabeza y cuello. Ensayo clínico controlado aleatorizado

Resumen Introducción: La ototoxicidad por cisplatino es un evento muy frecuente y sus consecuencias producen mucho deterioro en los pacientes. El diagnóstico precoz es esencial, pues permitiría implementar apropiadamente estrategias para aminorar su efecto. Entre estas tenemos la N-acetilcisteína, un agente antioxidante que ha demostrado efecto otoprotector. Objetivo: Evaluar el rol otoprotector de N-acetilcisteína comparado con placebo, en pacientes con cáncer de cabeza y cuello tratados con cisplatino. Material y Método: Ensayo clínico aleatorizado, paralelo y controlado con placebo. Se incluyen pacientes con cáncer de cabeza y cuello que requieren tratamiento con cisplatino, dos ramas: un grupo control que recibe placebo y otro que recibe el fármaco. Se realizan audiometrías de altas frecuencias (6-16 kHz) antes, durante y una vez finalizado el tratamiento. Resultados: Se aleatorizaron 45 pacientes, 23 al grupo intervencional y 22 al grupo control. Se encontró una incidencia general de la ototoxicidad del 73%, un empeoramiento en relación con tiempo de medición, una detención y estabilización del efecto ototóxico en el grupo que recibió N-acetilcisteína, todas estas diferencias fueron significativas. Conclusión: La N-acetilcisteína no previene la ototoxicidad inducida por cisplatino, pero modifica su curso de instalación y progresión. No se registraron efectos adversos al uso del fármaco. El monitoreo audiológico precoz es esencial para identificar la ototoxicidad y ejercer acciones para modificar su curso y mejorar la calidad de vida.

Abstract Introduction: Cisplatin-induced ototoxicity is a very frequent event and its consequences can cause a lot of deterioration in patients. There are some strategies to reduce its effect, among these, N-acetylcysteine, an antioxidant agent, has shown otoprotective effect. Aim: To evaluate the effect of N-acetylcysteine on ototoxicity by chemotherapy-radiotherapy in patients with head and neck cancer, compared with placebo. Material and Method: Randomized, parallel design and placebo controlled clinical trial. Patients with head and neck cancer who require treatment with cisplatin were enrolled: a control group that receives a placebo and experimental group that receives the drug. High-frequency audiometries were performed before, during and after the treatment finalization. Results: Forty-five patients were randomized, 23 for the experimental group and 22 for control group. The investigators found an incidence of ototoxicity of 73%, a worsening in relation to the time of measurement and a stopping and stabilization of the ototoxic effect in the group that received N-acetylcysteine, all these differences were statistically significant. Conclusion: N-acetylcysteine does not prevent cisplatin-induced ototoxicity, but does modify its course of installation and progression. No adverse effects were registered in this trial. Early audiological monitoring is essential to identify ototoxicity and eventually modify its course and improve the quality of life.

Cohortes de premedicación en endoscopia alta con simeticona, N-acetilcisteína, Hedera helix y validación de la escala visual / Cohorts of premedication for endoscopy of the upper gastrointestinal tract with simethicone, N-acetylcysteine, Hedera helix and visual scale validation

Resumen Los parámetros de calidad para endoscopia digestiva alta han introducido indicadores intraprocedimiento, dentro de los cuales la adecuada visibilidad de la mucosa, libre de saliva, moco o burbujas, puede aumentar la posibilidad de detección de lesiones en fase temprana. Sin embargo, el uso de mucolíticos y antiburbujas ha mostrado gran variabilidad de eficiencia según las soluciones, concentraciones, tiempos de exposición y escala de visibilidad aplicados. Objetivos: determinar la efectividad de diferentes soluciones de premedicación para la limpieza de la mucosa digestiva; validar, mediante una prueba de concordancia interobservador, una nueva escala de adecuada visualización de la mucosa (TVMS) para el esófago, estómago y duodeno; y reportar eventos adversos o complicaciones relacionadas con las soluciones utilizadas y los procedimientos realizados. Material y métodos: estudio de cohortes prospectivas comparativas. Se incluyeron 412 pacientes adultos, ASA I y ASA II, para endoscopia diagnóstica bajo sedación consciente, distribuidos en 6 cohortes similares, divididas en dos grupos: no premedicación, 2 cohortes C1 (ayuno de 6 a 8 horas)y C2 (agua 100 mL); premedicación, 4 cohortes C3 a C6 (C3: agua 100 m L + simeticona 1000 mg; C4: agua 100 mL + simeticona 200 mg + N-acetilcisteína 600 mg; C5: agua 100 mL + simeticona 200 mg + N-acetilcisteína 1000 mg; C6: agua 100 mL + simeticona 200 mg + Hedera helix 70 mg). Se ingirió la solución 15 a 30 minutos antes del paso por cricofaríngeo. Se realizó la prueba de Kappa para medir la concordancia interobservador de la escala TVMS. Resultados: De 412 pacientes, 58% fueron de sexo femenino; 23% (136) fue de cohortes C1 y C2 y 67% (276) fue de cohortes C3 a C6. El tiempo medio de exposición a cada solución fue de 24,4 minutos. El volumen de lavado para lograr una adecuada visualización fue significativamente diferente entre ambos grupos: en los pacientes con premedicación se utilizaron 75,6 mL, mientras que en los pacientes sin premedicación se utilizaron 124 mL (p = 0,000), con una calidad de TVMS excelente de 88,7% frente al 41,4%, respectivamente. La cohorte C4 (agua 100 mL + simeticona 200 mg + N-acetilcisteína 600 mg) mostró ser la más efectiva con una diferencia significativa (p = 0,001) frente a C1 (ayuno) y C2 (placebo con agua 100 mL), y también tuvo una eficiencia superior frente a C3, C5 y C6 en su orden. No se presentaron eventos adversos o complicaciones en relación con la endoscopia, la sedación y los productos usados en la premedicación. Conclusiones: la solución más efectiva como premedicación para lograr una excelente visibilidad de la mucosa digestiva correspondió a la cohorte C4 (SIM 200 + NAC 600 + H2O 100 mL). La escala TVMS propuesta es una herramienta muy completa y fácil de aplicar por más de un observador. La premedicación ingerida, con antiburbuja, mucolítico y agua hasta 100 mL, entre 15 y 30 minutos previos a endoscopia, es segura en las condiciones descritas en este estudio.

Abstract Quality parameters for upper gastrointestinal endoscopy have introduced intraprocedural indicators, including adequate mucosal visualization free of saliva, mucus, or bubbles, which may increase the possibility of early-stage injury detection. The use of mucolytics and anti-foaming agents has shown great efficiency variability depending on the type of solution, concentrations, exposure times and visibility scale applied. Objectives: To determine the effectiveness of different premedication solutions for cleaning the digestive mucosa; to validate, by means of an interobserver concordance test, a new scale for the adequate visualization of the mucosa (TVMS) for the esophagus, stomach, and duodenum; and to report adverse events or complications associated with the solutions used and the procedures performed. Material and methods: Prospective, comparative cohort study. 412 adult patients, ASA I and ASA II, were included for diagnostic endoscopy under conscious sedation. They were distributed in 6 similar cohorts and divided into two groups: non-premedication, 2 in C1 (fasting 6 to 8 hours) and C2 (water 100 mL) cohorts; premedication, 4 C3 to C6 cohorts (C3: water 100 mL + simethicone 1000 mg; C4: water 100 ml + simethicone 200 mg + N-acetylcysteine 600 mg; C5: water 100 ml + simethicone 200 mg + N-acetylcysteine 1000 mg; C6: water 100 ml + simethicone 200 mg + Hedera helix 70 mg). The solution was swallowed 15 to 30 minutes passing through the cricopharyngeus muscle. The Kappa test was performed to measure interobserver concordance of the TVMS scale. Results: Of 412 patients, 58% were female; 23% (136) were included in the C1 and C2 cohorts; and 67% (276) were in the C3 to C6 cohorts. The average exposure time to each solution was 24.4 minutes. The wash volume for proper visualization was significantly different between the two groups. In premedicated patients, 75.6 mL of solution were used, while in patients without premedication, 124 mL were used (p = 0.000), with an excellent quality of TVMS of 88.7% versus 41.4%, respectively. The C4 cohort (water 100 mL + simethicone 200 mg + N-acetylcysteine 600 mg) was the most effective with a significant difference (p= 0.001) compared with the C1 (fasting) and C2 (placebo with water 100 mL) cohorts. It also had better efficiency compared to the C3, C5 and C6 cohorts in that order. There were no adverse events or complications associated with endoscopy, sedation, or premedication products. Conclusions: The most effective solution as a premedication to achieve excellent visibility of the digestive mucosa was that used in the C4 cohort (SIM 200 + NAC 600 + H2OR 100 mL). The proposed TVMS scale is a very complete and easy tool to apply by more than one observer. Premedication ingested, with anti-foam, mucolytic and water up to 100 mL, between 15 and 30 minutes before endoscopy, is safe under the conditions described in this study.

The Study of Estrous Cycle Phases Female Rats With the Use of N-Acetylcysteine in Ovarian Graft / Estudo do Ciclo Estral de Ratas com Uso de N-Acetilcisteína no Enxerto Ovariano

Ovarian graft may be the target of the biochemical effects of oxidative stress caused at the time of transplantation. In order to evaluate the effect of N-acetylcysteine on the ovarian graft, regarding the estrous cycle preservation, 50 female and virgin EPM-1 Wistar rats, weighing up to 250g, originating from CEDEME of UNIFESP, were kept in adequate sanitary conditions. receiving their own food and water. Daily vaginal smears were performed to identify the estrous phase for 8 days. The animals were randomly distributed into 05 groups: 1st Group (GTx), saline was administered subcutaneously, 2nd (NAC 150mgKg), 3rd (NAC 300mg / Kg), 4th (NAC 600mg / Kg) and 5th (NAC 1200mg / Kg), that were administered NAC subcutaneously on the abdominal face, 60 minutes before left unilateral ovarian transplantation in retr operitoneum and contralateral oophorectomy for purposes of histomorphological analysis, with colpocytological evaluation. Euthanasia was performed by means of anesthetic lethal dose in half of the animals on the 4th postoperative day, with a single vaginal smear collection and euthanasia on the rest of the animals, between the 14th and 16th days, after the material was collected in order to define the estrus phase. It was evaluated in the graft that the animals exhibited in all groupsreturn of estrous cycle in the later phase of the post-transplant, with better definition of regular cycle in the highest dosages of N-acetylcysteine. N-acetylcysteine induced the return of the estrous cycle in the rats' ovarian graft , mainly in the highest dosage, proving its effectiveness in revascularization of the tissue after ischemia and reperfusion. (AU)

O enxerto ovariano pode ser alvo dos efeitos bioquímicos do stress oxidativo causado no momento do transplante. Com o objetivo de avaliar o efeito da N-acetilcisteína no enxerto ovariano, quanto à preservação do ciclo estral, foram utilizados 50 ratos EPM-1 Wistar, fêmeas e virgens, pesando até 250g, originários do CEDEME da UNIFESP, mantidos em adequadas condições sanitárias, recebendo ração própria e água. Realizados esfregaços vaginais diários para identificação da fase estral durante 08 dias. Os animais foram distribuídos aleatoriamente em 05 grupos: 1º Grupo (GTx), administrada solução salina via subcutânea, 2º (NAC 150mgKg), 3º (NAC 300mg/Kg), 4º (NAC 600mg/Kg) e 5º (NAC 1200mg/Kg), aos quais foi administrada NAC por via subcutânea em face abdominal, 60 minutos antes do transplante unilateral esquerdo do ovário em retroperitônio e à ooforectomia contra-lateral para fins de análise histomorfológica, com avaliação colpocitológica. A eutanásia foi realizada por meio da dose letal do anestésico em metade dos animais no 4º dia de pós-operatório, realizado única coleta de esfregaço vaginal e a eutanásia no restante dos animais, entre o 14 º e 16º dia, após a coleta do material para definição da fase estro . Foi avaliado no enxerto que os animais apresentaram em todos os grupos retorno de ciclo estral na fase mais tardia do pós-transplante, com melhor definição de ciclo regular nas dosagens mais elevadas de N-acetilcisteína. A N-acetilcisteína induziu o retorno do ciclo estral no enxerto ovariano de ratas, principalmente na maior dosagem comprovando sua eficácia na revascularização do tecido após isquemia e reperfusão. (AU)

N-acetylcysteine maintains penile length and erectile function in bilateral cavernous nerve crush rat model by reducing penile fibrosis / 亚洲男科学杂志(英文版)

Penile length shortening and erectile dysfunction are common complications after radical prostatectomy. Various methods have been used to maintain erectile function, but less attention has been paid to preserving penis length. N-acetylcysteine (NAC) has the effect of antioxidation and antifibrotic, which may be beneficial to improve those postoperative complications. This study investigated the effect of NAC on maintaining the penile length and the erectile function after bilateral cavernous nerve crush (BCNC) and its underlying mechanism. Twenty-four male rats were randomly divided into three groups: control group, BCNC group, and BCNC + NAC group. NAC or equal volume of saline was daily administrated by intragastric gavage for 4 weeks. The initial and end penile lengths were measured. Intracavernosal pressure/mean arterial pressure (ICP/MAP) ratio was calculated to assess erectile function. Hematoxylin-eosin staining, Masson's trichrome staining, immunohistochemistry, and Western blot were performed to explore cellular and molecular changes of the penis. Compared to the BCNC group, the penile length, ICP/MAP ratio and smooth muscle/collagen ratio in the BCNC + NAC group were improved significantly (all P < 0.05), and the expressions of endothelial nitric oxide synthase, α-smooth muscle actin, glutathione, and glutathione peroxidase 1 were significantly increased after NAC treated (all P < 0.05), along with the decreased expressions of hypoxia-inducible factor-1α, transforming growth factor-β1, collagen I, collagen III, collagen IV, malonaldehyde, and lysine oxidase (all P < 0.05). This study demonstrated that NAC could maintain penile length and partly improve erectile function. Possible mechanism is directly and/or indirectly related to antihypoxic and antifibrosis.

N-acetylcysteine as an adjunctive treatment for smoking cessation: a randomized clinical trial

Objective: This randomized controlled trial examined the efficacy and safety of N-acetylcysteine as an adjunctive treatment for smoking cessation. Methods: Heavy smokers were recruited from smoking cessation treatment for this 12- week randomized controlled trial. Eligible tobacco use disorder outpatients (n=34) were randomized to N-acetylcysteine or placebo plus first-line treatment. Abstinence was verified by exhaled carbon monoxide (COexh). The assessment scales included the Fagerström Test for Nicotine Dependence, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Minnesota Nicotine Withdrawal Scale, and the Medication Adherence Rating Scale. We also assessed anthropometrics, blood pressure, lipid profile, and soluble tumor necrosis factor receptor (sTNF-R) levels 1 and 2. Results: First-line treatment for smoking cessation plus adjunctive N-acetylcysteine or placebo significantly reduced COexh (p < 0.01). In the N-acetylcysteine group, no significant changes were found in nicotine withdrawal symptoms, depressive and anxiety symptoms, anthropometric measures, blood pressure, or glucose compared to placebo. However, there was a significant reduction in sTNF-R2 levels between baseline and week 12 in the N-acetylcysteine group. Conclusions: These findings highlight the need to associate N-acetylcysteine with first-line treatment for smoking cessation, since combined treatment may affect inflammation and metabolism components. Clinical trial registration: NCT02420418

Review of Aluminium Phosphide Poisoning

Agricultural revolution and increasing pesticidal use have brought its share of downsides in the form of pesticidal poisoning. Every year approximately 300,000 deaths happen worldwide due to pesticide poisoning. Organophosphates, chlorates, and aluminum phosphide are the commonly used pesticides. Alkaline phosphatase (ALP) is the most lethal among the available pesticides and no antidote is available and aptly called as suicide poison. The common use and easy availability of ALP is causing acute and chronic health effects which have reached major proportions in Asian and Middle Eastern countries such as India, Bangladesh, Iran, Jordan, and Sri Lanka. Toxicity of ALP is related to prompt release of lethal phosphine gas as ALP tablet absorbs moisture. Phosphine gas mainly affects cardiovascular system gastrointestinal tracts, lungs, and kidneys. The clinical features of poisoning include nausea, vomiting, abdominal pain, pulmonary edema, cyanosis shock arrhythmias, and alter sensorium. Diagnosis of ALP poisoning largely depends on history and clinical setting and treatment is usually initiated without waiting for silver nitrate paper test or gastric aspirate analysis. Treatment includes early gastric lavage symptomatic supportive therapy and palliative care. There has been greater understanding about the mechanism and pathophysiology of ALP toxicity over the years, although that cannot be commented about the treatment modalities. Government efforts to restrict sale have been offset by the lack of strict enforcement by regulatory agencies. Case fatality rates from ALP poisoning have shown some decline over the years due to early supportive management. Different treatment modalities and protocols have been tried at various centers with variable success; however, further research for an antidote is the need of the hour.

La N-acetilcisteína reduce el progreso de daño cardíaco en modelos experimentales / N-acetylcysteine reduces myocardial injury progression in experimental models

RESUMEN La N-acetilcisteína es conocida en varias especialidades médicas. Su empleo en cardiología se ha incrementado desde hace décadas, por su potencial para disminuir el impacto del daño por reperfusión en el infarto miocárdico agudo. Pero el espectro de sus efectos es aún mayor, tiene acciones sobre los radicales de oxígeno, con un papel protector, por la vía de los grupos sulfhidrilos de regiones importantes de la membrana celular, los cuales interfieren y tienen efecto en la función endotelial y en los procesos complejos de adhesión como efectos secundarios; así como otros fenómenos del compartimento extravascular. Estos procesos están estrechamente relacionados con el aparato cardiovascular.

ABSTRACT N-acetylcysteine is known in a number of medical specialties and its ability to decrease the impact of reperfusion injury in acute myocardial infarction has boosted its use in cardiology over the past decades. N-acetylcysteine has a far-reaching range of effects since it functions as a protective agent against oxygen radicals through sulfhydryl groups in important regions of the cell membrane that interfere and affect endothelial functioning and complex adhesion processes as side effects; as well as other phenomena of the extravascular compartment. These processes are closely related to the cardiovascular system.

Role of N-acetyl cysteine on bone marrow-derived hematopoietic stem/progenitor cell cryopreservation: Outcome on the oxidative stress-mediated cryodamage and repopulation Capacity into hematopoietic lineages

Cryopreservation of hematopoietic stem/progenitor cells (HSPCs) is associated with oxidative stress-mediatedcryodamage, hence compromising the therapeutic potency. The roles of N-acetyl cysteine (NAC) on the oxidativestress-mediated cryodamage and repopulation capacity of HSPCs into myeloid, erythroid, and pre-B lymphoidprogenitors were investigated. Mice bone marrow-derived HSPCs were cultured for 24 hours, followed bycryopreservation at 1 × 106/ml cells in cryomedium containing 10% dimethyl sulfoxide with NAC (0.25, 0.5, or 2.0µM) or without for 48 hours, 2 weeks, and 4 weeks at −80°C. Cryopreservation significantly reduced cell viability atpost-thawed (p < 0.05) with long-term cryopreservation conferred a greater cell recovery. NAC improved the bonemarrow-derived HSPC viability (p < 0.05) at 0.5 and 2.0 µM after 48 hours of cryopreservation. Cryopreservationlowered the malondialdehyde level (p < 0.05) although glutathione, superoxide dismutase, and protein carbonyl levelswere not significantly affected. Repopulation capacity of HSPCs into myeloid–erythroid progenitors was greatlyreduced (p < 0.05) after 4 weeks of cryopreservation as compared to precryopreservation group. Meanwhile, NACsupplementation showed no remarkable effect on oxidative stress-mediated cryodamage and repopulation capacity ofHSPCs. Conclusively, the cryoprotective role of NAC on the cryopreservation of HSPCs deserves further investigation

Protective effect of N-acetylcysteine against cisplatin ototoxicity in rats: a study with hearing tests and scanning electron microscopy / Efeito protetor da N-acetilcisteína na ototoxicidade por cisplatina em ratos: um estudo com testes auditivos e microscopia eletrônica de varredura

Abstract Introduction Ototoxicity is a health problem appearing after powerful treatments in serious health conditions. It is sometimes inevitable when treatment of the serious disease is required. Cisplatin is an antineoplastic agent which was investigated previously to reveal increased nitrogen and reactive oxygen radicals that damages hair cells, resulting in ototoxicity. N-acetylcysteine, previously shown to decrease ototoxicity caused by different agents, is known to be a powerful in vitro antioxidant. Probably N-acetylcysteine, in addition to its antioxidant effect, blocks a cascade where reactive oxygen species result in apoptosis in the cochlea. Objectives The possible preventive effect of N-acetylcysteine in cisplatin ototoxicity was studied with auditory brain stem responses, otoacoustic emissions, and histopathological investigation of the cochlea in a scanning electron microscopy. Methods This study was conducted on 21 Wistar Albino rats in four groups. 1 mL/kg/day three times in total intraperitoneal (i.p.) Saline (n = 5), 500 mg/kg/day i.p. three times in total N-acetylcysteine (n = 5), i.p. 15 mg/kg cisplatin alone (single dose) (n = 5) and i.p. 15 mg/kg cisplatin plus 500 mg/kg/day N-acetylcysteine (n = 6) were administered. The rats were anesthetized to study the hearing tests before and after the experiment. The rats were sacrificed to investigate the cochleas by scanning electron microscopy. Results Auditory brain stem responses and otoacoustic emissions values were attenuated in the cisplatin group. The group that received N-acetylcysteine in addition to cisplatin had better auditory brain stem responses thresholds and otoacoustic emissions. The samples obtained from the cisplatin group showed surface irregularities, degeneration areas, and total or partial severe stereocilia losses. The changes were milder in the cisplatin + N-acetylcysteine group. Conclusion Cisplatin ototoxicity can be detected by auditory brain stem responses and otoacoustic emissions testing in rats. N-acetylcysteine may protect the cochlear cells from histopathological changes. We concluded that N-acetylcysteine given 4 h after cisplatin injection has a potential otoprotective effect against cisplatin ototoxicity. which suggests it could be used in clinical trials.

Resumo Introdução A ototoxicidade é um problema que pode ocorrer após certos tipos de tratamentos para condições graves de saúde. Às vezes é inevitável quando o tratamento da doença é necessário. A cisplatina é um agente antineoplásico cujo uso em pesquisas anteriores demonstrou aumentar os radicais livres de nitrogênio e espécies reativas de oxigênio que danificam as células ciliadas e resultam em ototoxicidade. Por outro lado, a N-acetilcisteína, que já demonstrou diminuir a ototoxicidade causada por diferentes agentes, é conhecida por ser um potente antioxidante in vitro. Provavelmente a N-acetilcisteína, além de seu efeito antioxidante, bloqueia uma cascata onde espécies reativas de oxigênio resultam em apoptose na cóclea. Objetivos Estudar o possível efeito preventivo da N-acetilcisteína na ototoxicidade por cisplatina por meio de potencial evocado auditivo de tronco encefálico, emissões otoacústicas e investigação histopatológica da cóclea por microscopia eletrônica de varredura. Método Este estudo foi realizado em 21 ratos albinos Wistar, separados em quatro grupos. Foram administrados: 1 mL/kg/dia intraperitoneal (i.p.) de solução salina (n = 5), três vezes no total; 500 mg/kg/dia i.p. de N-acetilcisteína (n = 5), três vezes no total; 15 mg/kg i.p. (dose única) somente de cisplatina (n = 5) e 15 mg/kg i.p. de cisplatina e 500 mg/kg/dia i.p. de N-acetilcisteína (n = 6). Os ratos foram anestesiados para estudo dos testes auditivos antes e depois do experimento. Os ratos foram sacrificados para investigação da cóclea por microscopia eletrônica de varredura. Resultados Os potenciais evocados auditivos de tronco encefálico e os valores das emissões otoacústicas estavam atenuados no grupo cisplatina. O grupo que recebeu N-acetilcisteína além da cisplatina apresentou melhores limiares de respostas auditivas do tronco encefálico e emissões otoacústicas. As amostras obtidas do grupo cisplatina apresentaram irregularidades de superfície, áreas de degeneração, com perdas graves totais ou parciais de estereocílios. As alterações foram mais leves no grupo cisplatina + N-acetilcisteína. Conclusão A ototoxicidade por cisplatina pode ser detectada por meio de potenciais evocados auditivos de tronco encefálico e pelo teste de emissões otoacústicas em ratos. A N-acetilcisteína pode proteger as células cocleares contra alterações histopatológicas. Concluímos que a N-acetilcisteína administrada 4 horas após a injeção de cisplatina tem potencial efeito otoprotetor contra a ototoxicidade por cisplatina e pode ser utilizada em ensaios clínicos.